US1941647A - Process for the manufacture of ether derivatives of 1-benzyl-3-methyl-isoquinoline - Google Patents
Process for the manufacture of ether derivatives of 1-benzyl-3-methyl-isoquinoline Download PDFInfo
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- US1941647A US1941647A US469262A US46926230A US1941647A US 1941647 A US1941647 A US 1941647A US 469262 A US469262 A US 469262A US 46926230 A US46926230 A US 46926230A US 1941647 A US1941647 A US 1941647A
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- Prior art keywords
- isoquinoline
- methyl
- acid
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- bases
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- 238000000034 method Methods 0.000 title description 10
- 238000004519 manufacturing process Methods 0.000 title description 9
- 150000002170 ethers Chemical class 0.000 title description 2
- 239000002585 base Substances 0.000 description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 238000006356 dehydrogenation reaction Methods 0.000 description 16
- 150000001408 amides Chemical class 0.000 description 15
- 238000010438 heat treatment Methods 0.000 description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
- 150000003840 hydrochlorides Chemical class 0.000 description 11
- 239000003513 alkali Substances 0.000 description 9
- 239000012458 free base Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 239000007795 chemical reaction product Substances 0.000 description 7
- 239000000155 melt Substances 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 7
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 7
- 238000000354 decomposition reaction Methods 0.000 description 5
- 229960001789 papaverine Drugs 0.000 description 5
- ODVLMCWNGKLROU-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)acetic acid Chemical compound OC(=O)CC1=CC=C2OCOC2=C1 ODVLMCWNGKLROU-UHFFFAOYSA-N 0.000 description 4
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000003610 charcoal Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229960003424 phenylacetic acid Drugs 0.000 description 3
- 239000003279 phenylacetic acid Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- YXWQTVWJNHKSCC-UHFFFAOYSA-N 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCN1 YXWQTVWJNHKSCC-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- -1 methyl papaverine Chemical compound 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical group C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 description 1
- XLAOKZDOZHZWBK-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)propan-2-ylazanium;chloride Chemical compound [Cl-].CC([NH3+])CC1=CC=C2OCOC2=C1 XLAOKZDOZHZWBK-UHFFFAOYSA-N 0.000 description 1
- OFJWFSNDPCAWDK-UHFFFAOYSA-N 2-phenylbutyric acid Chemical compound CCC(C(O)=O)C1=CC=CC=C1 OFJWFSNDPCAWDK-UHFFFAOYSA-N 0.000 description 1
- FVVXWRGARUACNW-UHFFFAOYSA-N 3-Methyl-isochinolin Natural products C1=CC=C2C=NC(C)=CC2=C1 FVVXWRGARUACNW-UHFFFAOYSA-N 0.000 description 1
- DTBDAFLSBDGPEA-UHFFFAOYSA-N 3-Methylquinoline Natural products C1=CC=CC2=CC(C)=CN=C21 DTBDAFLSBDGPEA-UHFFFAOYSA-N 0.000 description 1
- QOQGCNATZUALDD-UHFFFAOYSA-N 7-methyl-[1,3]dioxolo[4,5-g]isoquinoline Chemical compound C1=C2C=NC(C)=CC2=CC2=C1OCO2 QOQGCNATZUALDD-UHFFFAOYSA-N 0.000 description 1
- BPMMUODPPJXZHI-UHFFFAOYSA-N C(CC1=CC(OC)=C(OC)C=C1)(=O)O.COC=1C=C(C=CC1OC)CC(=O)O Chemical compound C(CC1=CC(OC)=C(OC)C=C1)(=O)O.COC=1C=C(C=CC1OC)CC(=O)O BPMMUODPPJXZHI-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241001072332 Monia Species 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- BQIKRTGTPBOIMK-UHFFFAOYSA-N [O]C[O] Chemical compound [O]C[O] BQIKRTGTPBOIMK-UHFFFAOYSA-N 0.000 description 1
- 150000000475 acetylene derivatives Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- ZHJMCJIZYGTPMH-UHFFFAOYSA-N chembl58067 Chemical compound OC1=C(O)C=C2C(C)=NC=CC2=C1 ZHJMCJIZYGTPMH-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
Definitions
- This invention relates to the manufacture of compounds of therapeutic value.
- the dehydrogenation may be carried out in an advantageous way only with palladium as catalyst.
- the reaction product which separates out as a dark partly crystalline mass, is separated from the toluene and stirred with parts of water and heated for half an hour, filtered with carbon and allowed to crystallize.
- the hydrochloride of the new base 100 separates off in prisms which melt at 237 C. with decomposition.
- the hydrochloride is separated by crystallization and sucking oil.
- the free base is obtained by adding alkali to the solution of the hydrochloride, taking the reaction product up with ether and evaporating the solution to crystallization. It melts at 103 C. 10 parts of the same are stirred with 1 part of palladium black for 3 hours at about 180 C. The fused mass is dissolved in hot 4 per cent hydrochloric acid, puri- 10 fied with charcoal and allowed to crystallize.
- the hydrochloride separates off in prisms which contain water of crystallization and melt in an anhydrous state at 254 C. (with decomposition).
- the free base crystallizes out from methanol in brilliant prisms having a melting point 141 C.
- reaction and structural formulas are illus- (2) 10 parts of the amide are dissolved in 150 parts of toluene with heating, and after the addition of a mixture of 10 parts of phosphorous pentoxide in 20 parts of toluene, the
- the free base is, as described in Example 1, dehydrogenated by heating with palladium.
- the average yield is 60%.
- the melting point of the new base is 109 C.
- the methylpapaverine is obtained by heating this oil with one-fourth part of its weight of palladium to about 180.
- the end product (methyl papaverine) melts, after redissolving fromalcohol, at 136.
- the hydrochloride crystallizes with water of crystallization. It is obtained in an anhydrous state by crystallizing from alcohol and melts at about 234 with decomposition. The average yield is 60%.
- methyl-papaverine is CIIHI (prepared from 1-(3'-4' -dimethoxyphenyl)-2- aminopropane and homopiperonylic acid having a melting point 110) are dissolved in 150 parts of xylene and, after the addition of 10 parts of phosphorous oxychloride, heated to C.
- the reaction product is worked up to the free base which is dehydrogenated by heating with 10% of palladium black to 190 C.
- the isoquinolinederivative is repurified from boiling ether.
- the base melts at 168-169 C.
- the hydrochloride (crystallized from absolute alcohol) melts at about 233 C. with decomposition.
- the average yield is 60%;. 125
- the reaction product is worked up to a free base, which is dehydrogenated with palladium black at about 180 C. and redissolved from alcohol.
- the substance separates in colorless leaflets which melt at 143.
- the hydrochloride is very diflicultly soluble in water and melts at about 80 C. Average yield is 70%.
- crysmethyl-6,7-dialkoxy-isoquinoline consisting in condensing phenylacetic acid and a 1-(3',4'-dialkoxyphenyl) -2-amino-propane, treating the amide thus obtained with phosphorus oxychloride talline hydrochlorides of the bases thus obtained; liberating the free bases from the hydrochlorides by the addition of alkali; and heating the bases with palladium black to about 180 C. for the purpose of dehydrogenation.
- each X is hydrogen or alkoxy or both 140
- each X is hydrogen or alkoxy or both stand for the methylenedioxy radical
- the Ys represent members of the group consisting of alkoxy and methylenedioxy
- the R stands for hydrogen or alkyl
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Description
UNITED STATES PATENT OFFICE PROCESS FOR THE MANUFACTURE OF ETHER DERIVATIVES OF 1 -BENZYL 3- METHYL-ISOQUINOLINE Otto Wolfes, Darmstadt, Germany No Drawing. Application July 19, 1930, Serial No. 469,262, and in Germany August 24, 1929 9 Claims.
This invention relates to the manufacture of compounds of therapeutic value.
It is known (Bischler 8a Napieralski, Ber. der
deutschen chem.
Gesellschaft 26 (1893) 1903,
Pictet & Finkelstein, Ber. d. deutschen chem. Gesellschaft 42 (1909) 1979) that acid amides which have been phenylacetic acids obtained by'the interaction of and l-phenyl 2 amino ethanes, can often be converted into l-benzyldihydro-isoquinolines under the influence of condensing agents such as zinc chloride, phosphorous pentoxide, phosphorous oxychloride.
That this reaction does not always take place,
but is influenced by certain groups of atoms, is
evident from a work by Callow, Gulland and Haworth (J ourn.
Chemic. Soc. London,-1929, p.
1444). An acetylene derivative having an open chain was obtainedinstead of the expected isoquinoline derivative. Gadamer, Oberlin, Schtiler (Archiv. d. Pharm.
Similarly experiments of 263 (1925) 3 para 2) met-with negative results. It was therefore not to be foreseen whether isoquinoline with an alkyl-group' in position 3 could beprepared according to the above mentioned process.
It has been found by experiment that acid amides which contain-asbasic components, for example, 1 (3,4 methylene dioxyphenyl) -2- amino-propane (German Patent 274,350) are able to close the dihydro-isoquinoline ring under the influence of condensing agents. If in this reaction the acid components are derivatives of phenyl-acetic acid or ethers of oxy derivatives of phenylacetic acid then bases of papaverine-like constitution and physiological action are obtained by dehydrogenation. Some of them are distinguished from papaverine by a more favorable therapeutic index. This was not to be expected because the compounds analogous to papaverine which were already known were not advantageous for medicinal purposes (Mannich 8; Walter, Archiv. d. Phar. 265 (1927) p. 3).
Furthermore it densation takes has been found that the con- 'place at temperatures from 150, the dehydrogenation takes place at 160-220"; more especially the most advantageous temperature for carrying out the condensation is about 105, while is carried out at the dehydrogenation preferably about 180 C. 9 Although any found that phosphorous oxychloride is the .most
suitable condensing agent. The pointed out temperatures of 105 condensing agent and 180 C. and. the mentioned together secure the best yields.
The dehydrogenation may be carried out in an advantageous way only with palladium as catalyst.
As already mentioned the new products are of especial therapeutic value. Particularly 1-(3,4- methylenedioxybenzyl) -3-methy1-6,7-methylene- 60 dioxyisoquinoline has proved to be of high pharmaceutical value. This compound is manufactured as shown in Example 1, shows a melting point of 141, is soluble in chloroform, hot alcohol and hot ether, difficulty soluble in cold alcohol 5 and cold ether, insoluble in water.
It was already known that diand tetrahydropapaverine can be dehydrogenated to papaverine by means of palladium (Spaeth u. Burger, Ber. der deutschen chem. Gesellschaft 60 (192"!) I04), but in this case both the carbon atoms, whose single bond is to be converted into a double bond, carry two hydrogen atoms. In the present case it is a question of dehydrogenation in which one of each of the hydrogen atoms is replaced by an alkyl group whereby the dehydrogenation could be made difiicult and in certain circumstances impossible. As to how little such dehydrogenations were to be foreseen according to literature up to the present, is shown by the 30 work of Shire Akabori and Tazo Suzuki (Proceed. Imp. Acad. Tokyo 5, 255) who were unable to dehydrogenate tetrahydropapaverine as is expressly mentioned by the authors.
Examples (1) 10 parts of the amide (011202) C6H3 CH2CH(CH3) -NH COCH2C6H3(O2 CH2) (prepared from 1-(3',4-methylenedioxyphenyl 2 aminopropane and homopiperonylic acid, melting point -146) are dissolved in 180 parts of hot toluene and heated with 6 parts of phosphorous oxychloride for 3 hours to'about 100 C. The reaction product, which separates out as a dark partly crystalline mass, is separated from the toluene and stirred with parts of water and heated for half an hour, filtered with carbon and allowed to crystallize. The hydrochloride of the new base 100 separates off in prisms which melt at 237 C. with decomposition. The hydrochloride is separated by crystallization and sucking oil. The free base is obtained by adding alkali to the solution of the hydrochloride, taking the reaction product up with ether and evaporating the solution to crystallization. It melts at 103 C. 10 parts of the same are stirred with 1 part of palladium black for 3 hours at about 180 C. The fused mass is dissolved in hot 4 per cent hydrochloric acid, puri- 10 fied with charcoal and allowed to crystallize. The hydrochloride separates off in prisms which contain water of crystallization and melt in an anhydrous state at 254 C. (with decomposition). The free base crystallizes out from methanol in brilliant prisms having a melting point 141 C.
The yield amounts to about 90% of the theoretioal on closing the ring and 75% of theoretical on dehydrogenation. v
The reaction and structural formulas are illus- (2) 10 parts of the amide are dissolved in 150 parts of toluene with heating, and after the addition of a mixture of 10 parts of phosphorous pentoxide in 20 parts of toluene, the
solution is boiled. After cooling the reaction product is stirred, after separation of the toluene, with 100 parts or" water, boiled with charcoal, filtered and the hydrochloride of the new base is separated out by adding common salt.
The temperatures used and other measures are the same as in Example 1.
The free base is, as described in Example 1, dehydrogenated by heating with palladium. The average yield is 60%. The melting point of the new base is 109 C.
The structural formula is as follows;
(3) 150 parts of the amide (CHaO) 2C6H3-CH2-CH(CH3) N'HCOCH2C6H3 (OCHa) 2 (prepared from 1-(3', 4-dimethoxy-phenyl-2- aminopropane and 3, 4 dimethoxyphenyl-acetic acid (homoveratric acid) are dissolved in 1500 parts of hot toluene and heated with 130 parts of phosphorous oxychloride for 6 hours to 100 C. After separating the toluene the reaction product is dissolved in hot water, filtered with charcoal and worked up to the free base by adding am,- monia solution. This base is obtained as a thick oil by taking up in ether, filtering with charcoal and distilling 011 the ether. The methylpapaverine is obtained by heating this oil with one-fourth part of its weight of palladium to about 180. The end product (methyl papaverine) melts, after redissolving fromalcohol, at 136. The hydrochloride crystallizes with water of crystallization. It is obtained in an anhydrous state by crystallizing from alcohol and melts at about 234 with decomposition. The average yield is 60%.
The structural formula of methyl-papaverine is CIIHI (prepared from 1-(3'-4' -dimethoxyphenyl)-2- aminopropane and homopiperonylic acid having a melting point 110) are dissolved in 150 parts of xylene and, after the addition of 10 parts of phosphorous oxychloride, heated to C. The reaction product is worked up to the free base which is dehydrogenated by heating with 10% of palladium black to 190 C. The isoquinolinederivative is repurified from boiling ether. The base melts at 168-169 C. The hydrochloride (crystallized from absolute alcohol) melts at about 233 C. with decomposition. The average yield is 60%;. 125
The structural formula is as follows: 7
CHaO- CHaO N Y.
J)Hz
(5) 10 parts of the amide sition. The average yield is 60%. 50'
(6) 10 parts of the amide (prepared from 1- (3' -4' -methylenedioxyphenyl- 2-aminopropane and ethyl phenylacetic acid,
melting point=l38 are dissolved in 20 parts of hot toluene and heated with 8 parts of phosphorous oxychloride for 3 hours to 105 C. The reaction product is worked up to a free base, which is dehydrogenated with palladium black at about 180 C. and redissolved from alcohol. The substance separates in colorless leaflets which melt at 143. The hydrochloride is very diflicultly soluble in water and melts at about 80 C. Average yield is 70%.
The structural formula is as follows:
/0 CHa H26 I I claim:
1. As a product 1-(3'4'-methylenedioxybenzyl) 3-methyl-6,7-methylenedioxyisoquinoline, a substance soluble in chloroform, hot alcohol and hot ether, difiicultly soluble in cold alcohol and cold ether, insoluble in water, showing a melting point of 141 C., while the hydrochloride of this base melts at 254 C. (under decomposition) the free base showing crystals of brilliant prisms.
2. Process for the production of a 1-benzyl-3- methyl-6,7-dialkoxy-isoquinoline consisting in condensing a phenylacetic acid with 1-(3,4'-dialkoxyphenyl)-2-amino-propane, treating the amide thus obtained with acid condensing agents at a temperature of about 60-150 0.; separating the crystalline hydrochlorides of the bases thus obtained; liberating the free bases from the hydrochlorides by the addition of alkali; and heating the bases with palladium black to about 160- 220 C. for the purpose of dehydrogenation.
3. Process for the production of a 1-(3',4-dialkoxy-benzyl) 3 methyl-6,7 -dialkoxy-isoquinoline consisting in condensing a 3,4-dialkoxyphenylacetic acid with a 1-(3,4'-dialkoxyphenyl)-2-amino-propane, treating the amide thus obtained with acid condensing agents at a temperature of about 60-150 C.; separating the crystalline hydrochlorides of the bases thus obtained; liberating the free bases from the hydrochlorides by the addition of alkali; and heating the bases with palladium black to about 160220 C. for
- V the purpose of dehydrogenation.
' at a temperature of 105 0.; separating the crysmethyl-6,7-dialkoxy-isoquinoline consisting in condensing phenylacetic acid and a 1-(3',4'-dialkoxyphenyl) -2-amino-propane, treating the amide thus obtained with phosphorus oxychloride talline hydrochlorides of the bases thus obtained; liberating the free bases from the hydrochlorides by the addition of alkali; and heating the bases with palladium black to about 180 C. for the purpose of dehydrogenation.
5. Process for the production of a 1-(3,4-dialkoxy-benzyl) -3 methyl-6,7-dihydroxy -isoquinoline consisting in condensing a 3,4-dialkoxyphenylacetic acid with a 1-(3',4-dialkoxyphenyl)-2-amino-propane, treating the amide thus obtainedwith phosphorus oxychloride at a tem-- perature of C., separating the crystalline hydrochlorides of the bases thus obtained; liberating the free bases from the hydrochlorides by the addition of alkali; and heating the bases with palladium black to about 180 C. for the purpose of dehydrogenation.
6. Process for the production of 1-(3',4- methylenedioxybenzyl) -3-methyl-6,7-methylenedioxy-isoquinoline, consisting in condensing homopiperonylic acid and 1-(3,4'-methylenedioxyphenyl) -2-amino-propane, treating the amide thus obtained with acid condensing agents at a temperature of 60150 0., separating the crystalline hydrochloride of the base formed in the preceding step, liberating the free base from the hydrochloride by the addition of alkali; and heating the base thus obtained with finely divided palladium black to 160-220" C. for the purpose of dehydrogenation.
7. Process for the production of 1-(3',4'- methylenedioxybenzyl) -3-methyl-6,7-methylenedioxy-isoquinoline, consisting in condensing homopiperonylic acid and 1-(3',4-methylenedioxyphenyl) -2-amino-propane, treating the amide thus obtained with phosphorus oxychloride at a temperature of 105 C., separating the crystalline hydrochloride of the base formed in the preceding step, liberating the free base from the hydrochloride by the addition of alkali; and heating the base thus obtained with finely divided palladium black to 180 C. for the purpose of dehydrogenation.
8. Process which consists in treating an amide of the type represented by the formula,
wherein each X is hydrogen or alkoxy or both 140,
at a temperature of about 60 C. to 150 C., sepai rating the crystalline hydrochlorides of the bases thus obtained, liberating the free bases from the hydrochlorides by the addition of alkali, and heating the bases with palladium black to about 160220 C; forthe purpose of dehydrogenation,
the product being represented by the general wherein each X is hydrogen or alkoxy or both stand for the methylenedioxy radical, and the Ys represent members of the group consisting of alkoxy and methylenedioxy, and the R stands for hydrogen or alkyl.
9. Process for the production of 1-(3',4'-dia1- koxybenzyl) 3 -methyl- 6,7-dia1koxy -isoquino1ine, consisting in condensing 3,4-dialkoxy-pheny1- acetic acid with 1- (3',4'-dia1koxypheny1) -2- amino-propane, treating the amide thus obtained with acid condensing agents at a temperature of about 60-150 C.; separating the crystalline hydrochloride of the base thus obtained; liberating the free bases from the hydrochlorides by the addition of alkali; and heating the bases with palladium black to about 160-220" C. for the purpose of dehydrogenation. V
OTTO WOLFES.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1941647X | 1929-08-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US1941647A true US1941647A (en) | 1934-01-02 |
Family
ID=7750509
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US469262A Expired - Lifetime US1941647A (en) | 1929-08-24 | 1930-07-19 | Process for the manufacture of ether derivatives of 1-benzyl-3-methyl-isoquinoline |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US1941647A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2608581A (en) * | 1949-12-30 | 1952-08-26 | Monsanto Chemicals | Preparation of n-(3, 4-dialkoxyphenylacetyl)-3', 4'-dialkoxyphenalkylamines |
| US2683713A (en) * | 1951-02-16 | 1954-07-13 | Lilly Co Eli | Substituted benzylisoquinolines |
| US2728769A (en) * | 1954-08-17 | 1955-12-27 | Lilly Co Eli | Alkoxybenzylisoquinolines and salts thereof |
| US2879293A (en) * | 1957-02-19 | 1959-03-24 | Hoffmann La Roche | Benzylamine derivatives |
-
1930
- 1930-07-19 US US469262A patent/US1941647A/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2608581A (en) * | 1949-12-30 | 1952-08-26 | Monsanto Chemicals | Preparation of n-(3, 4-dialkoxyphenylacetyl)-3', 4'-dialkoxyphenalkylamines |
| US2683713A (en) * | 1951-02-16 | 1954-07-13 | Lilly Co Eli | Substituted benzylisoquinolines |
| US2728769A (en) * | 1954-08-17 | 1955-12-27 | Lilly Co Eli | Alkoxybenzylisoquinolines and salts thereof |
| US2879293A (en) * | 1957-02-19 | 1959-03-24 | Hoffmann La Roche | Benzylamine derivatives |
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